Xr. Kong et al., Sarcolemmal and mitochondrial K-ATP channels mediate cardioprotection in chronically hypoxic hearts, J MOL CEL C, 33(5), 2001, pp. 1041-1045
Hypoxia from birth increases the resistance of the isolated neonatal heart
to ischemia. We determined if increased resistance to ischemia was due to a
ctivation of sarcolemmal or mitochondrial K channels. Rabbits (n=8/group) w
ere raised from birth in a normoxic (F1O2 = 0.21) or hypoxic (F1O2 = 0.12)
environment for 8-10 days and the heart perfused with Krebs-Henscleit bicar
bonate buffer. A mitochondrial-selective K-ATP, channel blocker 5-hpdroxyde
canoate (5-HD) (300 mu mol/l) or a sarcolcmmal-selective K-ATP, channel blo
cker HMR 1098 ( 30 mu mol/l) were added alone or in combination for 20 min
prior to a global ischemic period of 30 min. followed by 35 min reperfusion
. Recovery of ventricular developed pressure R as higher in chronically hyp
oxic than normoxic hearts. 5-HD and HMR 1098 partially reduced the cardiopr
otective effect of chronic hypoxia, but had no effect in normoxic hearts. T
he combination of 5-HD and HMR 1098 abolished the cardioprotective effect o
f chronic hypoxia. We conclude that both sarcolemmal and mitochondrial K-AT
P channels contribute to cardioprotection in the chronically hypoxic heart.
(C) 2001 Academic Press.